scholarly journals The role of a new ALK isoform in the diagnosis and targeted therapy of skin melanoma

2021 ◽  
Vol 20 (4) ◽  
pp. 33-41
Author(s):  
K. S. Titov ◽  
A. A. Markin ◽  
A. M. Kazakov ◽  
S. V. Chulkova
Keyword(s):  
Targeted Therapy ◽  
Checkpoint Inhibitors ◽  
Braf Inhibitor ◽  
Routine Practice ◽  
Targeted Drugs ◽  
Skin Melanoma ◽  
Anaplastic Lymphoma ◽  
Number Of Patients ◽  
The World

Contemporary discoveries of fundamental science in recent decades in the field of oncology have led to the emergence of new highly effective anticancer drugs: targeted drugs and immune checkpoint inhibitors, use of which has made a breakthrough in the treatment of oncological diseases, including skin melanoma. Melanoma is still one of the most cancerous tumors. The number of patients resistant to targeted therapy and immunotherapy increases in the world every year. Oncologists have practically no leverage to influence the disease after the development of resistance to this type of therapy. In this regard, scientists around the world are looking for new application points for targeted drugs. Nowadays, the most common treatment method is BRAF inhibitors, since the BRAF mutation is detected in 40–60 % of patients with skin melanoma. However, the resistance to BRAF inhibitor therapy occur in half cases after 6–8 months. To overcome the resistance to the target therapy is one the most important issue, the studying of new isoform of anaplastic lymphoma kinase (ALK) may help to solve this problem.Purpose of the study – to order the data of the leading researchers of a new isoform of ALK, and reveal the most promising directions for its further progress.In the article, there are comparisons and analyses the 6 of the largest studies over the past 5 years devoted to a new isoform of ALK.The joint inhibition of the new ALK isoform and BRAFV600 showed positive results in several studies with different levels of ALKATI expression (alternative initiation of ALK transcription). The new ALK isoform can stimulate oncogenesis only within a certain “threshold” level of expression. Immunohistochemical examination cannot be the main method for determining the expression of a new ALK isoform due to low sensitivity. In almost all studies, tumors with ALK translocation responded to therapy with ALK inhibitors.Even though that the role of the new ALK isoform has been studied in recent years, the optimal method for evaluating the expression of ALKATI in routine practice has not yet been determined. Additional studies are also needed to understand the effectiveness of the use of ALК inhibitors in combination with BRAF and ERK inhibitors. Of interest is the blockade of extracellular vesicles and the study of the role of interleukin-3 in the inhibition of ALKATI.

scholarly journals Response to Ipilimumab/Nivolumab Rechallenge and BRAF Inhibitor/MEK Inhibitor Rechallenge in a Patient with Advanced Metastatic Melanoma Previously Treated with BRAF Targeted Therapy and Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Caitlyn N. Myrdal ◽  
Srinath Sundararajan
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Optimal Sequencing ◽  
The Right

Little is known about the optimal sequencing of targeted therapy and immunotherapy in the treatment of patients with BRAFV600-mutated metastatic melanoma. BRAF/MEK inhibition often has the benefit of rapid disease regression; however, resistance is frequently seen with long-term use. Treatment with immune checkpoint inhibitors offers the potential for long-term response but displays a lower rate of objective response. The benefit of synergy between therapies is apparent; however, there is limited data regarding optimal sequencing in the treatment of advanced melanoma. We present the case of a 62-year-old gentleman with advanced BRAFV600-mutated melanoma who followed an unconventional treatment path. After progressing on single-agent vemurafenib, he had response to multiple modalities of immunotherapy before progression. After, he had a substantial response to multiple BRAF/MEK inhibitor rechallenges before developing resistance. The patient is now stable after a retrial of combination immunotherapy. Our case illustrates that with the right sequencing of therapy, meaningful clinical responses can be elicited with rechallenging of targeted therapy and immunotherapy in metastatic melanoma.

Controversies in the Management of Advanced Melanoma

2014 ◽  
Vol 48 (11) ◽  
pp. 1456-1468 ◽  
Author(s):  
Anthony Jarkowski ◽  
LeAnn Norris ◽  
Van Anh Trinh
Keyword(s):  
Targeted Therapy ◽  
Disease Progression ◽  
English Language ◽  
Cytotoxic T Lymphocyte ◽  
Data Extraction ◽  
Braf Inhibitor ◽  
Advanced Melanoma ◽  
Braf Inhibitors ◽  
Treatment Sequencing

Objective: To examine the current controversies and discuss consensus recommendations regarding treatment sequencing and the role of BRAF inhibitor at disease progression. Data Source: An English-language literature search of MEDLINE/PubMed (1966-May 2014), using the keywords advanced melanoma, ipilimumab, cytotoxic T-lymphocyte antigen 4, dabrafenib, vemurafenib, BRAF inhibitor, trametinib, MEK inhibitor, and treatment sequencing was conducted. Data were also obtained from package inserts, meeting abstracts, and clinical registries. Study Selection and Data Extraction: All relevant published articles and abstracts on ipilimumab, vemurafenib, dabrafenib, and trametinib were reviewed. Clinical trial registries and meeting abstracts were used for ongoing studies. Data Synthesis: The availability of new agents has made therapy selection more complex. Immunotherapy supporters reason that immunotherapy offers the best chance for long-term benefit and does not compromise the antitumor activity of subsequent BRAF inhibitors. Targeted therapy advocates rely on the high probability and rapid onset of response to BRAF inhibitors. Currently, there is insufficient evidence regarding the role of BRAF inhibitor at disease progression. Conclusions: Therapy should be individualized based on patient- and disease-specific factors. Immunotherapy represents the best option for durable remission; however, targeted therapy is more appropriate for patients who are symptomatic or have rapidly growing tumors. The novel therapies have also demonstrated meaningful intracranial activity; thus, the presence of brain metastases should be taken into consideration in selecting therapy. Limited data exist about the continuation of BRAF inhibitors after therapeutic failure. Active research is ongoing to define the best option for patients with BRAF inhibitor refractory disease.

scholarly journals Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma—A Retrospective Multicenter ADOReg Study

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2312
Author(s):  
Henner Stege ◽  
Maximilian Haist ◽  
Michael Schultheis ◽  
Maria Isabel Fleischer ◽  
Peter Mohr ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Checkpoint Inhibitors ◽  
Patient Characteristics ◽  
Complete Response ◽  
Second Line ◽  
Treatment Cessation ◽  
Durable Response ◽  
Ongoing Treatment ◽  
Number Of Patients ◽  
The Impact

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.

Making sense of the Global Coronavirus Data: The role of testing rates in understanding the pandemic and our exit strategy (Preprint)

2020 ◽  
Author(s):  
Rahul Potluri ◽  
Deepthi Lavu
Keyword(s):  
Large Scale ◽  
Population Level ◽  
Death Rates ◽  
Social Instability ◽  
Making Sense ◽  
Number Of Patients ◽  
The World ◽  
Inherent Case ◽  
Early Indication

BACKGROUND The Coronavirus disease 2019(COVID-19) outbreak has caused havoc across the world. Subsequently, research on COVID-19 has focused on number of cases and deaths and predicted projections have focused on these parameters. We propose that the number of tests performed is a very important denominator in understanding the COVID-19 data. OBJECTIVE We analysed the number of diagnostic tests performed in proportion to the number of cases and subsequently deaths across different countries and projected pandemic outcomes. METHODS We obtained real time COVID-19 data from the reference website Worldometer at 0900 BST on Saturday 4th April, 2020 and collated the information obtained on the top 50 countries with the highest number of COVID 19 cases. We analysed this data according to the number of tests performed as the main denominator. Country wise population level pandemic projections were extrapolated utilising three models - 1) inherent case per test and death per test rates at the time of obtaining the data (4/4/2020 0900 BST) for each country; 2) rates adjusted according to the countries who conducted at least 100000 tests and 3) rates adjusted according to South Korea. RESULTS We showed that testing rates impact on the number of cases and deaths and ultimately on future projections for the pandemic across different countries. CONCLUSIONS We found that countries with the highest testing rates per population have the lowest death rates and give us an early indication of an eventual COVID-19 mortality rate. It is only by continued testing on a large scale that will enable us to know if the increasing number of patients who are seriously unwell in hospitals across the world are the tip of the iceberg or not. Accordingly, obtaining this information through a rapid increase in testing globally is the only way which will enable us to exit the COVID-19 pandemic and reduce economic and social instability. CLINICALTRIAL Not applicable

Electrospinning: New Strategies for the Treatment of Skin Melanoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Javier Mauricio Anaya Mancipe ◽  
Franz Acker Lobianco ◽  
Marcos Lopes Dias ◽  
Rossana Mara da Silva Moreira Thiré
Keyword(s):  
United States ◽  
Skin Cancer ◽  
The United States ◽  
World Population ◽  
Skin Melanoma ◽  
The World ◽  
Northern Regions ◽  
Common Skin ◽  
New Strategies

: Recent studies have shown significant growth of skin cancer cases in northern regions of the world, in which its presence was not common. Skin cancer is one of the cancers that mostly affects the world population, ranking fifth in studies conducted in the United States (USA). Melanoma is cancer that has the highest number of deaths worldwide since it is the most resistant skin cancer to current treatments. This is why alternatives for its treatment have been investigated considering nanomedicine concepts. This study approaches the role of this field in the creation of promising electrospun devices, composed of nanoparticles and nanofibers, among other structures, capable of directing and/or loading active drugs and/or materials with the objective of inhibiting the growth of melanoma cells or even eliminating those cells.

scholarly journals The Role of Obesity in Renal Cell Carcinoma Patients: Clinical-Pathological Implications

2019 ◽  
Vol 20 (22) ◽  
pp. 5683 ◽  
Author(s):  
Gaetano Aurilio ◽  
Francesco Piva ◽  
Matteo Santoni ◽  
Alessia Cimadamore ◽  
Giulia Sorgentoni ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Renal Cell Carcinoma ◽  
Adipose Tissue ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Rcc

Obesity is a well-known risk factor for renal cell carcinoma (RCC) development. However, the RCC–obesity link has not been fully addressed when considering a comprehensive scenario starting from pathogenetic aspects through pathological issues up to the outcome of medical treatment. We therefore conducted an electronic PubMed search using keywords “obesity”, “body mass index”, “overweight”, “renal cell carcinoma/kidney cancer”, “medical treatment”, “targeted therapy”, and “immunotherapy/immune checkpoint inhibitors”. The selected data supported a crosstalk between adipose tissue (adipocytes and other white adipose tissue cells) and cancer cells inducing several signaling pathways that finally stimulated angiogenesis, survival, and cellular proliferation. Accurate sampling of renal sinus fat correlated with a prognostic value. Retrospective clinical evidence in metastatic RCC patients with higher body mass index (BMI) and treated with targeted therapies and/or immune checkpoint inhibitors showed advantageous survival outcomes. Therefore, obesity may influence the course of RCC patients, although the interplay between obesity/BMI and RCC warrants a large prospective confirmation. We are therefore still far from determining a clear role of obesity as a prognostic/predictive factor in metastatic RCC patients undergoing targeted therapy and immunotherapy.

scholarly journals Making sense of the Global Coronavirus Data: The role of testing rates in understanding the pandemic and our exit strategy

2020 ◽  
Author(s):  
Rahul Potluri ◽  
Deepthi Lavu
Keyword(s):  
Large Scale ◽  
Population Level ◽  
Death Rates ◽  
Social Instability ◽  
Making Sense ◽  
Number Of Patients ◽  
The World ◽  
Inherent Case ◽  
Early Indication

AbstractThe Coronavirus disease 2019(COVID-19) outbreak has caused havoc across the world. Subsequently, research on COVID-19 has focused on number of cases and deaths and predicted projections have focused on these parameters. We propose that the number of tests performed is a very important denominator in understanding the COVID-19 data. We analysed the number of diagnostic tests performed in proportion to the number of cases and subsequently deaths across different countries and projected pandemic outcomes.We obtained real time COVID-19 data from the reference website Worldometer at 0900 BST on Saturday 4th April, 2020 and collated the information obtained on the top 50 countries with the highest number of COVID 19 cases. We analysed this data according to the number of tests performed as the main denominator. Country wise population level pandemic projections were extrapolated utilising three models - 1) inherent case per test and death per test rates at the time of obtaining the data (4/4/2020 0900 BST) for each country; 2) rates adjusted according to the countries who conducted at least 100000 tests and 3) rates adjusted according to South Korea.We showed that testing rates impact on the number of cases and deaths and ultimately on future projections for the pandemic across different countries. We found that countries with the highest testing rates per population have the lowest death rates and give us an early indication of an eventual COVID-19 mortality rate. It is only by continued testing on a large scale that will enable us to know if the increasing number of patients who are seriously unwell in hospitals across the world are the tip of the iceberg or not. Accordingly, obtaining this information through a rapid increase in testing globally is the only way which will enable us to exit the COVID-19 pandemic and reduce economic and social instability.

scholarly journals Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Claudia Trojaniello ◽  
Jason J. Luke ◽  
Paolo A. Ascierto
Keyword(s):  
Targeted Therapy ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Hdac Inhibitors ◽  
Oncolytic Viruses ◽  
Current Status ◽  
Specific Gene ◽  
Number Of Patients ◽  
Car T ◽  
History Of

Melanoma is the most fatal skin cancer. In the early stages, it can be safely treated with surgery alone. However, since 2011, there has been an important revolution in the treatment of melanoma with new effective treatments. Targeted therapy and immunotherapy with checkpoint inhibitors have changed the history of this disease. To date, more than half of advanced melanoma patients are alive at 5 years; despite this breakthrough, approximately half of the patients still do not respond to treatment. For these reasons, new therapeutic strategies are required to expand the number of patients who can benefit from immunotherapy or combination with targeted therapy. Current research aims at preventing primary and acquired resistance, which are both responsible for treatment failure in about 50% of patients. This could increase the effectiveness of available drugs and allow for the evaluation of new combinations and new targets. The main pathways and molecules under study are the IDO inhibitor, TLR9 agonist, STING, LAG-3, TIM-3, HDAC inhibitors, pegylated IL-2 (NKTR-214), GITR, and adenosine pathway inhibitors, among others (there are currently about 3000 trials that are evaluating immunotherapeutic combinations in different tumors). Other promising strategies are cancer vaccines and oncolytic viruses. Another approach is to isolate and remove immune cells (DCs, T cells, and NK cells) from the patient’s blood or tumor infiltrates, add specific gene fragments, expand them in culture with growth factors, and re-inoculate into the same patient. TILs, TCR gene transfer, and CAR-T therapy follow this approach. In this article, we give an overview over the current status of melanoma therapies, the clinical rationale for choosing treatments, and the new immunotherapy approaches.

scholarly journals Pendampingan Mitigasi dan Adaptasi Perilaku Baru di Masa Pandemi Covid-19 Melalui Gerakan Masyarakat Menggunakan Masker (GEMAS), Penggunaan Antiseptik dan Desinfektan di Kabupaten Bombana, Sulawesi Tenggar

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Nuralifah ◽  
Ruslin ◽  
Andi Nafisah Tendri Adjeng ◽  
Yuni Aryani Koedoes ◽  
Nur Fitriana Muhammad Ali
Keyword(s):  
Population Density ◽  
Global Health ◽  
Community Service ◽  
Public Knowledge ◽  
Hand Sanitizer ◽  
The People ◽  
Number Of Patients ◽  
The World ◽  
Global Health Problem

COVID-19 causes worldwide panic and become a global health problem so that it is declared as pandemic since December 2019. Indonesia is a country with 4th population density in the world. The level of spread of COVID-19 patients in Indonesia may be more than countries with smaller populations. South East Sulawesi has confirmed 484 of COVID-19 cases. One of the highest areas with the number of patients is Bombana Regency. The purpose of community service carried out by lecturers and students from Halu Oleo University was to strengthen the role of the people of Bombana Regency in mitigating and adapting to the COVID-19 pandemic. Activities in community service included education and socialization of GEMAS, antiseptics, and disinfectants which were carried out offline (door to door) and online. As well as the distribution of masks and spray hand sanitizer for free. Through this activity, it can be expected to increase public knowledge and awareness in using masks, antiseptics, and disinfectants properly to face COVID-19 pandemic.

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